Influence of fluvoxamine on carvedilol's pharmacokinetics in rats

Abstract

Carvedilol is one of the most used cardiovascular drugs, highly metabolized by CYP450 2D6, 1A2, 2C9. Fluvoxamine, an antidepressant agent, is a moderate/potent inhibitor of these enzymes. There is the risk of drug-drug interaction when these two drugs are concomitantly administered. The aim of this study was to investigate the drug-drug interactions between carvedilol and fluvoxamine in rats. There were two periods: reference and test. In the first period each rat received an oral dose of 3.57 mg/kg body weight carvedilol. In the test period, carvedilol was administered after a pre-treatment with multiple oral doses of fluvoxamine (14.28 mg/kg b.w.). HPLC-MS was used to determine the plasma concentration of carvedilol. The PK parameters were calculated by non-compartmental analysis. Fluvoxamine co-administered with carvedilol can change the PK parameters (increase AUC, t1/2, decrease the Cl). The present study demonstrated the pharmacokinetic drug-drug interaction between carvedilol and fluvoxamine in vivo.